Eyes are the windows of a body, open to the external world and rich in nutrients, helping a living being to perceive the surrounding environment. Consequently, eyes are vulnerable to virulent microorganisms, the invasion and uncontrolled growth of which causes various types of ophthalmic infections, for instance, blepharitis, conjunctivitis and keratitis.
The common types of microorganisms causing ophthalmic infections are viruses, bacteria, and fungi. These microorganisms may directly invade the surface of the eye, or permeate into the globe of the eye through trauma or surgery, or transmit into the eye through the blood stream or lymphatic system as a consequence of a systemic disease. The microorganisms may attack any part of the eye structure, including the conjunctiva, the cornea, the uvea, the vitreous body, the retina, and the optic nerve.
Ophthalmic infections can cause severe pain, swollen and red tissues in or around eyes, and blurred or decreased vision and warrant immediate medical treatment. However, before the nature of the microorganism causing the infections is first determined, initial treatment options at the onset of the infections are usually very limited, since the differentiation of a bacteria-caused ophthalmic infection from virus-caused or fungi-caused infection on the basis of clinical observation is frequently not reliable. Leibowitz et al., Human Conjunctivitis: Diagnostic Evaluation, Arch. Ophthalmol. 94: 1747–1749 (1976). Once the microorganism data are available after days of the infections, the ophthalmic infections can then be treated with pertinent antimicrobial agents, including antiviral agents, antibacterial agents or antifungal agents, individually or in combination.
The antiviral agents commonly used in treating ophthalmic infections are Idoxurine and Acyclovir. Idoxurine inhibits the replication of viral DNA and is effective against Herpes simplex virus (HSV). However, studies have shown that Idoxurine is toxic to corneal epithelial cells and if the treatment continues for longer than a week it may cause punctate lesions to develop. Lazarus et al., An in vitro Method Which Assesses Corneal Epithelial Toxicity due to Antineoplastic, Apreservative and Antimicrobial Agents, Lens Eye Toxic. Res. 6: 59–85 (1989). Acyclovir inhibits DNA replication of Herpes zoster virus (HZV) and therefore is commonly used to HZV-caused blepharitis or keratitis. However, it has been reported that Acyclovir has little or no preventative effect on the ocular complications of HZV. Aylad et al., Influence of Oral Acyclovir on Ocular Complications of Herpes zoster ophthalmicus, Eye 8: 70–74 (1994).
The majority of bacteria-caused ophthalmic infections are treated with topically applied ophthalmic antibacterial agents, including sulphonamide, tetracycline, chloramphenicol, aminoglycoside, beta-lactam, vancomycin, and fluoroquinolone. Leeming, Treatment of Ocular Infections with Topical Antibacterials, Clin. Pharmacokinet. 37: 351–360 (1999). However, considerable resistance to the antibacterial agents has been reportedly developed in bacteria. Studies have shown that 75% of ocular Staphylococcus species are resistant to tetracycline. Doughtery et al., The Role of Tetracycline in Chronic Blepharitis: Inhibition of Lipase Production in Staphylococcus, Inv. Ophthalmol. Vic. Sci. 32: 2970–2975 (1991). Flavobacterium indologenes is now resistant to most antibacterial agents. Lu & Chan, Flavobacterium indoloqenes Keratitis, Ophthalmologica 211: 98–100 (1997). Streptococcus pneumoniae and some strains of pneunococcus are resistant to penicillin. Wilkins et al., Penicillin-Resistant Streptococcus pneumoniae Keratitis, Cornea 15: 99–100 (1996). Approximately one third of Staphylococcus strains are resistant to gentamycin. Huberspitz et al., Corneal Ulceration: An Update from a Specialized Ambulatory Care Centre, Klinische. Monals. Augen. 200: 251–256 (1992). Additionally, 50% of bacteria isolated from corneal ulcers are resistant to all the common antibacterial agents. Satpathy & Vishalakshi, Ulcerative Keratitis: Microbial Profile and Sensitivity Pattern: A Five Year Study, Ann. Ophthalmol. Glaucoma 27: 301–306 (1995).
Antifungal agents are classified into two groups: polyenes such as amphotericin-B and azoles such as fluconazole. However, amphotericin-B is reported to have poor penetration into ocular tissues and show toxicity against eyes. Ishibashi & Kaufman, The Effects of Subconjunctival Miconozole in the Treatment of Experimental Candida Keratitis in Rabbits, Arch. Ophthalmol. 103: 1570–1573 (1985). Resistance to azoles and amphotericin-B has also been reported. Armstrong, The microbiology of the Eye, Ophthal. Physiol. Opt. 20: 429–503 (2000).
Given that the toxicity and resistance are commonly associated with the treatment of ophthalmic infections using the existing antimicrobial agents, it is desirable to provide a method for the treatment of ophthalmic infections using an inventive antimicrobial agent to reduce or minimize the toxicity and resistance. It is also desirable to provide a method for the treatment of an ophthalmic infection using an inventive antimicrobial agent that has antiviral, antibacterial and antifungal properties and can be used to treat the ophthalmic infection immediately after the onset of the infection without first taking days to determine the nature of microorganism causing the infection.